MalariaPhase 1NCT02554799
A Study to Evaluate the Pharmacokinetics of Oral Formulations of MMV390048 Administered Fasted to Healthy Volunteers
A Phase 1 study testing MMV390048 formulation A and MMV390048 formulation B in people with Malaria, run by Medicines for Malaria Venture at 1 site in United Kingdom.
Trial summary
This study will be conducted in a single centre, as an open single dose two parallel cohorts design with oral doses of MMV390048 administered in healthy male and female subjects between 18 to 55 years of age. Subjects will be screened within 28 days prior to entering the study. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- MMV390048 formulation A and MMV390048 formulation B
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 17 Sep 2015to 28 Oct 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- healthy male or female (non-childbearing potential) of any race, aged 18 to 55 years
- body weight at least 50kg and a body mass index 18 to 30Kg/m2
- Females must be of non-childbearing potential:
- Natural (spontaneous) post-menopausal defined (amenorrheic for at least 12 months without an alternative medical cause with a screening follicle stimulating hormone level >25IU/L (for post-menopause).
- Premenopausal with irreversible surgical sterilization by hysterectomy
- and/or bilateral oophorectomy or salpingectomy at least 6 months before screening
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- Males agree to use acceptable methods of contraception if the male subject's partner could become pregnant from the time of study medication until 120 days after administration of study medication. One of the following acceptable methods of contraception must be used:
- Condom and occlusive cap (diaphragm or cervical/vault cap) with spermicidal foam/gel/film/cream/suppository
- Surgical sterilization (vasectomy with documentation of azoospermia) and an acceptable barrier method (condom or occlusive cap [diaphragm or cervical/vault cap] used with spermicidal foam/gel/film/cream/suppository)
- subject's female partner uses oral contraceptives (combination estrogen / progesterone pills), injectable progesterone or sub-dermal implants and an acceptable barrier method
- subject's female partner uses medically prescribed topically applied transdermal contraceptive patch and an acceptable barrier method
- subject's female partner has undergone documented tubal ligation (female sterilization). In addition, an acceptable barrier method must be used.
- subject's female partner has undergone documented placement of an intrauterine device or intrauterine system. In addition, an acceptable barrier method must be used.
- True abstinence: when in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Abstinent subjects have to agree to use 1 of the above-mentioned contraceptive methods, if they start sexual relationships during the study and for up to 120 days post-study drug
- non-smokers or ex-smokers for more than 90 days prior to screening or smoke no more than 5 cigarettes per day. If users of nicotine products (spray, patch, e-cigarette, etc.) they should use the equivalent of no more than 5 cigarettes /day
- Subjects should not donate egg or sperm from the time of administration of study medication until 120 days post-study drug
- capable of fully understanding and complying with the requirements of the study and must sign the informed consent form prior to undergoing any study-related procedures
- agree to avoid excessive UV radiation exposure (occupational exposure to the sun, sunbathing, tanning salon use, phototherapy, etc.) throughout the study.
Who cannot join
- Male subjects with a female partner(s) who is (are) pregnant or lactating from the time of study medication
- Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means
- Current or recurrent disease (e.g. cardiovascular, neurological, renal, gastrointestinal, oncologic or other conditions) that may affect the action, absorption or disposition of the study medication or could affect clinical assessments or clinical laboratory evaluations
- Current or relevant history of physical or psychiatric illness that may require treatment or make the subject unlikely to fully comply with the requirements or complete the study, or any condition that presents undue risk from the investigational product or study procedures
- Any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of the participation in the study, may influence the result of the study, or the subject's ability to participate in the study
- History of photosensitivity
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- History or clinical evidence of alcohol or substance abuse. Alcohol abuse is defined as regular weekly intake of more than 21 units for males and 14 units for females
- Any clinically relevant history of intolerance/allergy to milk or dairy products
- Use of an investigational product or participation in a clinical study within 90 days before study medication
- Donation of blood products or of more than 500ml of blood in 90 days prior to study medication
- Use of any prescription drugs within 14 days or within 5 times the elimination half-life (whichever period is longer) prior to study medication
- Use moderate or strong inhibitors and/or inducers of CYP450/Transporters within 4 weeks prior to study drug administration (or 5 half-lives of the compound if longer)
- Use of over-the-counter medications or dietary supplements, including vitamins and herbal supplements within 7 days of study drug. With the exception of paracetamol which may be used incidentally or for short-term treatment at a maximum of 2g/day
- Intake of grapefruit, grapefruit juice or other products containing grapefruit within 28 days prior to study drug
- Excessive intake of caffeine drinks or energy drinks within 48 hours before admission (more than three 250ml cups of coffee a day, equivalent to roughly 250mg caffeine)
- Any clinically significant abnormal laboratory, vital signs or other safety findings as determined by medical history, physical examination or other evaluations at screening or admission.
- Any liver function tests elevated >1.5 times the upper limit of normal, considered by the investigator as clinically relevant, at screening or admission
- Abnormal serum Hemoglobin, Haptoglobin, Reticulocyte count or Lactate Dehydrogenase at screening/admission
- abnormal ECG results at screening/admission results considered as clinically significant by the investigator
- Confirmed positive urine drug screen (amphetamines, benzodiazepines, cocaine, cannabinoids, opiates, barbiturates or methadone) or from the alcohol breath test at screening/admission.
- positive human immunodeficiency virus, hepatitis B surface antigen, anti Hepatitis core antibody, or hepatitis C virus antibody at screening
- veins unsuitable for intravenous puncture or cannulation on either arm (e.g. veins difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture) 23. Any conditions which in the opinion of the investigator would make the subject unsuitable for enrolment or could interfere with the subjects' participation in or completion of the study
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Richmond Pharmacology Ltd.
Croydon, London, CR7 7YE
About this study
Official title: A Phase 1 Exploratory Study to Evaluate the Pharmacokinetics of Selected Oral Formulations of MMV390048 Administered in the Fasted State to Healthy Volunteers
This study will be conducted in a single centre, as an open single dose two parallel cohorts design with oral doses of MMV390048 administered in healthy male and female subjects between 18 to 55 years of age. Subjects will be screened within 28 days prior to entering the study. On Day 1 of the study each subject will receive one of the two MMV390048 prototype formulations, at a dose of 40 mg with 240 mL of water. Subjects will be discharged on Day 3 after 48h post-dose and they will attend the unit for follow-up visits on Days 5, 7, 10, 14, 19, 26 and 29.
Read the detailed description
A Phase 1 exploratory study to evaluate the pharmacokinetics of selected oral formulations of MMV390048 administered in healthy volunteers. It is anticipated that eighteen (18) healthy male and female subjects are to be included in the study, however there is an option to include an additional cohort of 9 subjects. The optional cohort would receive a single dose of the formulation considered to have the least pharmacokinetic variability with a suitable safety and tolerability profile with food or milk. Timing of PK samples may be adjusted in accordance with evolving data and dosing schedule. Additional or fewer PK samples may be taken in accordance with evolving data and dosing schedule to establish full protocol specific PK profile. The study specific maximum blood volume taken will not be exceeded.
- Conditions
- Malaria
- Being tested
- MMV390048 formulation A, MMV390048 formulation B
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MMV390048 formulation ADrug
MMV390048 formulation A, tablet
MMV390048 formulation BDrug
MMV390048 formulation B, tablet
| Study group | Role | What they receive |
|---|---|---|
| 40 mg MMV390048 tablet formulation A fasted | Experimental | 40 mg MMV390048 tablet formulation A, in fasted state Receives: Drug: MMV390048 formulation A |
| 40 mg MMV390048 tablet formulation B fasted | Experimental | 40 mg MMV390048 tablet formulation B fasted Receives: Drug: MMV390048 formulation B |
| 40 mg MMV390048 formulation A or B, with milk or fasted | Experimental | Optional cohort: 40 mg of MMV390048 in the formulation that has been shown to have the most favourable PK profile, taken with milk or in the fed state. Receives: Drug: MMV390048 formulation A; Drug: MMV390048 formulation B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax: Peak Plasma Concentration
Maximum concentration (Cmax) of two MMV390048 prototype formulations administered in the fasted state
Measured: Up to 672 hours post-dose
Tmax: Time to Reach Peak Plasma Concentration
Time to reach maximum plasma concentration (Tmax) of two MMV390048 prototype formulations administered in the fasted state
Measured: Up to 672 hours post-dose
AUC: Area Under the Plasma Concentration-time Curve From Zero to Infinity
Area under the plasma concentration-time curve (AUC) of two MMV390048 prototype formulations administered in the fasted state
Measured: From Pre-dose to 672 hours post-dose
Terminal Elimination Half-life (t1/2)
Terminal elimination half-life (t1/2) of two MMV390048 prototype formulations administered in the fasted state
Measured: Up to 672 hours post-dose
Terminal Elimination Rate Constant (Lambda z)
Terminal elimination rate constant (lambda z) of two MMV390048 prototype formulations administered in the fasted state
Measured: Up to 672 hours post-dose
Oral Plasma Clearance (CL/F)
Oral plasma clearance (CL/F) of two MMV390048 prototype formulations administered in the fasted state
Measured: Up to 672 hours post-dose
Apparent Volume of Distribution (Vz/F)
Apparent volume of distribution (Vz/F) of two MMV390048 prototype formulations administered in the fasted state
Measured: Up to 672 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2015 (estimated)
- Study start17 Sep 2015
- Primary completion28 Oct 2015
- Study completion28 Oct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medicines for Malaria Venture
- Sponsor type
- University, hospital or other
- Collaborators
- Richmond Pharmacology Limited
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02554799
- Sponsor's protocol ID
- MMV_MMV390048_15_01
- Status last verified
- Aug 2019
- First submitted
- 16 Sep 2015
- Last updated
- 10 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Sinxadi P, Donini C, Johnstone H, Langdon G, Wiesner L, Allen E, Duparc S, Chalon S, McCarthy JS, Lorch U, Chibale K, Mohrle J, Barnes KI. Safety, Tolerability, Pharmacokinetics, and Antimalarial Activity of the Novel Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048 in Healthy Volunteers. Antimicrob Agents Chemother. 2020 Mar 24;64(4):e01896-19. doi: 10.1128/AAC.01896-19. Print 2020 Mar 24.
PubMed 31932368
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Exploratory Study to Evaluate the Pharmacokinetics of Selected Oral Formulations of MMV390048 Administered in the Fasted State to Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02554799
- Acronym / sponsor ID
- MMV_MMV390048_15_01
- Conditions
- Malaria
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Medicines for Malaria VentureUniversity, hospital or other
- Collaborators
- Richmond Pharmacology Limited
- Study start
- 17 Sep 2015 (actual)
- Primary completion
- 28 Oct 2015 (actual)
- Study completion
- 28 Oct 2015 (actual)
- First posted
- 18 Sep 2015 (estimated)
- Results
- Posted 28 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will be conducted in a single centre, as an open single dose two parallel cohorts design with oral doses of MMV390048 administered in healthy male and female subjects between 18 to 55 years of age. Subjects will be screened within 28 days prior to entering the study. On Day 1 of the study each subject will receive one of the two MMV390048 prototype formulations, at a dose of 40 mg with 240 mL of water. Subjects will be discharged on Day 3 after 48h post-dose and they will attend the unit for follow-up visits on Days 5, 7, 10, 14, 19, 26 and 29.
Detailed description
A Phase 1 exploratory study to evaluate the pharmacokinetics of selected oral formulations of MMV390048 administered in healthy volunteers. It is anticipated that eighteen (18) healthy male and female subjects are to be included in the study, however there is an option to include an additional cohort of 9 subjects. The optional cohort would receive a single dose of the formulation considered to have the least pharmacokinetic variability with a suitable safety and tolerability profile with food or milk. Timing of PK samples may be adjusted in accordance with evolving data and dosing schedule. Additional or fewer PK samples may be taken in accordance with evolving data and dosing schedule to establish full protocol specific PK profile. The study specific maximum blood volume taken will not be exceeded.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 40 mg MMV390048 tablet formulation A fasted | Experimental | Drug: MMV390048 formulation A40 mg MMV390048 tablet formulation A, in fasted state |
| 40 mg MMV390048 tablet formulation B fasted | Experimental | Drug: MMV390048 formulation B40 mg MMV390048 tablet formulation B fasted |
| 40 mg MMV390048 formulation A or B, with milk or fasted | Experimental | Drug: MMV390048 formulation A, Drug: MMV390048 formulation BOptional cohort: 40 mg of MMV390048 in the formulation that has been shown to have the most favourable PK profile, taken with milk or in the fed state. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- healthy male or female (non-childbearing potential) of any race, aged 18 to 55 years
- body weight at least 50kg and a body mass index 18 to 30Kg/m2
- Females must be of non-childbearing potential:
- Males agree to use acceptable methods of contraception if the male subject's partner could become pregnant from the time of study medication until 120 days after administration of study medication. One of the following acceptable methods of contraception must be used:
- non-smokers or ex-smokers for more than 90 days prior to screening or smoke no more than 5 cigarettes per day. If users of nicotine products (spray, patch, e-cigarette, etc.) they should use the equivalent of no more than 5 cigarettes /day
Key exclusion criteria (22 listed)
- Male subjects with a female partner(s) who is (are) pregnant or lactating from the time of study medication
- Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means
- Current or recurrent disease (e.g. cardiovascular, neurological, renal, gastrointestinal, oncologic or other conditions) that may affect the action, absorption or disposition of the study medication or could affect clinical assessments or clinical laboratory evaluations
- Current or relevant history of physical or psychiatric illness that may require treatment or make the subject unlikely to fully comply with the requirements or complete the study, or any condition that presents undue risk from the investigational product or study procedures
- Any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of the participation in the study, may influence the result of the study, or the subject's ability to participate in the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MMV390048 formulation AMMV390048 formulation A, tablet | Drug | 40 mg MMV390048 formulation A or B, with milk or fasted, 40 mg MMV390048 tablet formulation A fasted |
| MMV390048 formulation BMMV390048 formulation B, tablet | Drug | 40 mg MMV390048 formulation A or B, with milk or fasted, 40 mg MMV390048 tablet formulation B fasted |
Primary outcome
Cmax: Peak Plasma Concentration
Time frame: Up to 672 hours post-dose
Maximum concentration (Cmax) of two MMV390048 prototype formulations administered in the fasted state
Tmax: Time to Reach Peak Plasma Concentration
Time frame: Up to 672 hours post-dose
Time to reach maximum plasma concentration (Tmax) of two MMV390048 prototype formulations administered in the fasted state
AUC: Area Under the Plasma Concentration-time Curve From Zero to Infinity
Time frame: From Pre-dose to 672 hours post-dose
Area under the plasma concentration-time curve (AUC) of two MMV390048 prototype formulations administered in the fasted state
Terminal Elimination Half-life (t1/2)
Time frame: Up to 672 hours post-dose
Terminal elimination half-life (t1/2) of two MMV390048 prototype formulations administered in the fasted state
Terminal Elimination Rate Constant (Lambda z)
Time frame: Up to 672 hours post-dose
Terminal elimination rate constant (lambda z) of two MMV390048 prototype formulations administered in the fasted state
Oral Plasma Clearance (CL/F)
Time frame: Up to 672 hours post-dose
Oral plasma clearance (CL/F) of two MMV390048 prototype formulations administered in the fasted state
Apparent Volume of Distribution (Vz/F)
Time frame: Up to 672 hours post-dose
Apparent volume of distribution (Vz/F) of two MMV390048 prototype formulations administered in the fasted state
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31932368Sinxadi P, Donini C, Johnstone H, Langdon G, Wiesner L, Allen E, Duparc S, Chalon S, McCarthy JS, Lorch U, Chibale K, Mohrle J, Barnes KI. Safety, Tolerability, Pharmacokinetics, and Antimalarial Activity of the Novel Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048 in Healthy Volunteers. Antimicrob Agents Chemother. 2020 Mar 24;64(4):e01896-19. doi: 10.1128/AAC.01896-19. Print 2020 Mar 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MMV390048 formulation A and MMV390048 formulation B in people with Malaria, run by Medicines for Malaria Venture at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cmax: Peak Plasma Concentration (time frame: Up to 672 hours post-dose). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02554799, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2019.